PCSK9: From Nature's Loss to Patient's Gain

The document discusses the impact of loss-of-function (LoF) mutations in the PCSK9 gene, which can lead to lower levels of low-density lipoprotein (LDL) cholesterol and significantly reduce the risk of major cardiovascular events, especially among Black individuals (2%). A study showed that individuals with these mutations had a 28% reduction in plasma LDL-C levels and an 88% reduction in major coronary events over 15 years. The document also highlights the development of anti-PCSK9 therapies, including a new antagonist, MK0616, which has shown promising results in clinical trials by significantly reducing plasma LDL-C levels. The safety and efficacy of PCSK9 inhibitors have been proven to be excellent, as predicted from human genetics.